Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania, USA.
Nat Struct Mol Biol. 2010 Apr;17(4):513-8. doi: 10.1038/nsmb.1777. Epub 2010 Mar 28.
Telomerase is a specialized DNA polymerase that extends the 3' ends of eukaryotic linear chromosomes, a process required for genomic stability and cell viability. Here we present the crystal structure of the active Tribolium castaneum telomerase catalytic subunit, TERT, bound to an RNA-DNA hairpin designed to resemble the putative RNA-templating region and telomeric DNA. The RNA-DNA hybrid adopts a helical structure, docked in the interior cavity of the TERT ring. Contacts between the RNA template and motifs 2 and B' position the solvent-accessible RNA bases close to the enzyme active site for nucleotide binding and selectivity. Nucleic acid binding induces rigid TERT conformational changes to form a tight catalytic complex. Overall, TERT-RNA template and TERT-telomeric DNA associations are remarkably similar to those observed for retroviral reverse transcriptases, suggesting common mechanistic aspects of DNA replication between the two families of enzymes.
端粒酶是一种特殊的 DNA 聚合酶，可延伸真核线性染色体的 3' 末端，这是基因组稳定性和细胞活力所必需的。在这里，我们展示了活性 Tribolium castaneum 端粒酶催化亚基 TERT 与一种 RNA-DNA 发夹的晶体结构，该发夹设计为类似于推定的 RNA 模板区域和端粒 DNA。RNA-DNA 杂交体采用螺旋结构，对接在 TERT 环的内部腔中。RNA 模板和模体 2 和 B'之间的接触将可及溶剂的 RNA 碱基定位在酶活性位点附近，用于核苷酸结合和选择性。核酸结合诱导刚性 TERT 构象变化，形成紧密的催化复合物。总体而言，TERT-RNA 模板和 TERT-端粒 DNA 的结合与逆转录病毒逆转录酶观察到的结合非常相似，这表明两种酶家族的 DNA 复制具有共同的机制方面。
